Background: Baxdrostat is a selective aldosterone synthase (CYP11B2) inhibitor for treatment‐resistant and uncontrolled hypertension, evaluated in phase 2/3 RCTs. Objectives: To estimate pooled placebo‐corrected reductions in seated office and ambulatory SBP, characterize the dose–response relationship, assess cortisol selectivity, and quantify hyperkalemia risk. Methods: We conducted a systematic review and meta‐analysis of phase 2/3 randomized, double‐blind, placebo‐controlled trials of baxdrostat in hypertension, searching MEDLINE/PubMed, EMBASE, ClinicalTrials.gov, and NEJM.org to March 2026. The primary outcome was placebo‐corrected change in seated office SBP, analyzed using random‐effects meta‐analysis (REML) with metafor in R. Risk of bias and certainty were evaluated using Cochrane RoB 2.0 and GRADE, respectively. Results: Three RCTs (BrigHTN, BaxHTN, Bax24; N = 1285) were included. The pooled seated SBP reduction was −9.44 mmHg (95% CI: −11.09 to −7.79; I ² = 0.0%), with dose subgroup estimates of −8.57 mmHg (1 mg) and −10.11 mmHg (2 mg) and a clear dose–response in BrigHTN (slope −4.2 mmHg/mg; R ² = 0.96). Bax24 demonstrated a 24 h ambulatory SBP reduction of −14.0 mmHg (95% CI: −17.2 to −10.8). Serum cortisol was unsuppressed at all doses, while the pooled OR for potassium ≥ 6.0 mmol/L was 5.14 (95% CI: 1.76 to 14.97). GRADE certainty was moderate for seated SBP, low to moderate for ambulatory outcomes, and low for hyperkalemia. Conclusions: Baxdrostat produces meaningful, selective BP reductions across hypertensive populations. Hyperkalemia is manageable with structured monitoring. Certainty is limited by a few trials, a short follow‐up, and safety imprecision. Long‐term cardiovascular outcome data are needed before guideline incorporation.

Background: Peripheral T-cell lymphoma (PTCL) has high relapse rates and poor response to various therapies. This meta-analysis evaluates the efficacy of various therapies for RR-PTCL, including Epigenetic modifiers (HDIs, DNA methyltransferase inhibitors, EZH1/2 inhibitors), Small molecule inhibitors (targeting PI3K/AKT/mTOR, JAK/STAT, ALK, aurora kinase, farnesyl transferase), Combination therapies (various multi-class drug combinations), Pralatrexate-based regimens, monoclonal antibodies (e.g., Pembrolizumab, Alemtuzumab, Zanolimumab, etc.) and Others (Acimtamig, CAR T-cell therapy, etc.). Aims: To evaluate pooled efficacy outcomes across therapeutic categories in relapsed/refractory peripheral T-cell lymphoma (RR-PTCL) by assessing overall response rate (ORR), complete response (CR), progression-free survival (PFS), and overall survival (OS), including analyses within major histologic subtypes. Methods: We systematically searched PubMed, Scopus, EMBASE, and Cochrane Library using MeSH terms for studies on RR PTCL. Eligible clinical trials reported at least one efficacy outcome. All statistical analysis was conducted using R (v4.5.3). Meta-analysis was performed to assess ORR and CR of each treatment. PFS and OS were summarized using weighted median survival estimates derived from the included studies and presented descriptively in forest plots. Formal pooled time-to-event meta-analysis was not performed. Subgroup analysis was done across PTCL-NOS, ALCL (ALK-), and AITL patient groups. Results: The study included 68 clinical trials, revealing significant influences of treatment type on both ORR (QM (df = 6) = 37.6, p < 0.001) and CR (QM (df = 6) = 36.7, p < 0.001). It demonstrated an overall ORR of 39.57% (95% CI: 0.36–0.43, p < 0.0001). Subgroup analyses for ORR with each treatment showed the highest rates with Combination therapies at 57.4% (95% CI: 0.50–0.65, p < 0.001), followed by Small molecule inhibitors (SMI) at 39.91% (p < 0.0001), Pralatrexate-based regimens at 39.5% (p < 0.001), Epigenetic modifiers at 39.1% (p < 0.001), Others at 34.7% (p < 0.001) and Monoclonal Antibodies showing the lowest at 31.9% (p < 0.0001). The pooled CR rate was 16.59% (95% CI: 0.14–0.19, p < 0.0001), with Combination therapies again leading at 32.0% (95% CI: 0.24–0.40, p < 0.001), followed by SMIs at 19.02%, Epigenetic modifiers at 16.0%, monoclonal antibodies at 11.6%, Pralatrexate-based regimens at 10.1%, and Others at 9.5% (all p < 0.001). Forest plots showed a pooled median OS of 14.6 months, highest with SMIs (17.9), followed by Pralatrexate (14.5), Combination therapies (14.4), Others (13.8), monoclonal antibodies (12.72), and Epigenetic modifiers (11.3). The pooled PFS was 4.18 months, led by Combination therapies (5.6), followed by Epigenetic modifiers (4), SMIs and Pralatrexate (3.5), Others (3.5), and monoclonal antibodies (2.7). Analysis by histological subtype, among PTCL-NOS and AITL subgroups, Combination Therapies showed highest ORR of 52.8% and 74.9% (both p < 0.001) respectively. Similar to ORR, in both subgroups, the highest incidence of CR was seen with Combination Therapy as 18.6% (95% CI: 0.082–0.29, p < 0.001) and 51.9% (95% CI: 0.31–0.73, p < 0.001). In ALCL (ALK-negative), pralatrexate-related regimens showed the highest ORR (56.44%, p = 0.0015), whereas therapeutic antibodies showed the highest CR (53.07%, p = 0.019). Conclusions: This analysis found that combination therapies demonstrated the highest pooled response rates, while small-molecule inhibitor and pralatrexate-based regimens were associated with the longest reported survival outcomes. The observed differences across therapeutic categories are descriptive and hypothesis-generating and warrant confirmation in prospective comparative studies. Despite recent therapeutic advances, outcomes in RR-PTCL remain suboptimal and novel treatment strategies continue to be needed.

Background: Ischemic heart disease (IHD) remains a leading cause of mortality in the United States, while arrhythmia‐related deaths are increasing. However, long‐term mortality trends involving both conditions remain unclear. Methods: We utilized the CDC WONDER Multiple Cause‐of‐Death database to obtain records from 1999 to 2023, targeting US adults aged ≥ 25 years. Deaths involving IHD and arrhythmias were assessed. Age‐adjusted mortality rates (AAMR) were calculated and stratified by gender, age, ethnicity, census region, and urbanization. Results: A total of 1 795 918 deaths were attributed to both IHD and cardiac arrhythmias between 1999 and 2023. The AAMR declined from 41.97 (95% CI: 41.66−42.27) in 1999 to 32.73 (95% CI: 32.51−32.94) in 2023, representing an overall decrease of 22% (AAPC −0.99). Men had higher AAMRs compared to women (45.0 [95% CI: 44.6−45.5] vs. 23.4 [95% CI: 23.2−23.7]). The highest mortality rate was observed among NH White individuals (AAMR: 34.8; 95% CI: 34.5−35.0), while the lowest was among NH Asian or Pacific Islanders (AAMR: 16.5; 95% CI: 15.6−17.5). Older adults exhibited the higher AAMRs (144.74; 95% CI: 143.60−145.88) compared to younger cohorts. An increased death burden was observed in non‐metropolitan (AAMR: 37.1; 95% CI: 36.5−37.8) and Midwest regions (35.5; 95% CI: 34.9−36.0). The majority of the deaths occurred in inpatient facilities (34.7%). Conclusions: Although IHD–arrhythmia mortality declined between 1999 and 2023, substantial disparities persisted across demographic and geographic subgroups, highlighting the need for targeted public health interventions.

Background: Alzheimer's disease (AD) among patients with metabolic syndrome-related conditions is a global threat, contributing significantly to escalating mortality and economic burden. They demonstrate analogous pathophysiologies and risk determinants, highlighting the necessity for addressing this critical issue. Objective: This study analyzed demographic trends and disparities of AD with metabolic syndrome-related conditions among patients aged 75 and above from 1999 to 2020. Methods: This study examined the death certificates sourced from the CDC-WONDER database from 1999 to 2020, to analyze age-adjusted mortality rates (AAMRs) per 100,000 population. The Joinpoint regression model was used to assess trends in overall demographics, geographic, and place-of-death variables. Results: There were 2,355,233 deaths documented with AD listed as the underlying cause of death among older adults (aged ≥75), out of which 444,488 deaths were related to metabolic syndrome-related conditions from 1999 to 2020. The AAMR rose substantially from 36.48 in 1999 to 157.93 in 2020. Women consistently had higher AAMRs than males (females: 107.79, males: 79.02). Non-Hispanic African Americans (121.65) showed the highest mortality rates among all racial groups. However, from 1999 to the early to mid-2000s, all races highlighted a sharp peak in mortality rates. Striking geographical disparities were noted, with Mississippi in the top 90 ^th percentile and Massachusetts in the lower 10 ^th percentile. Conclusions: This study reveals the demographic and geographic variations in mortality rates, highlighting the modalities of interventions and the need for equitable healthcare access.

Background: Cardiac arrest (CA) is one of the main causes of death in the U.S., and its impact on the healthcare system may be associated with substance-use (SU) disorders through the interplay of metabolic and cardiotoxic mechanisms. Despite the extensive research on drug overdose-related mortality, the impact of drug use on mortality from CA has not been thoroughly examined. Methods: We utilized the CDC WONDER Multiple Cause of Death database (1999–2023) to extract mortality data related to CA and SU-related causes of death among individuals aged ≥25 years. Age-adjusted mortality rates (AAMRs) per 100 000 were computed. Temporal trends were assessed using Joinpoint to calculate annual percent changes (APCs) along with 95% confidence intervals. Rates were stratified by sex, race, age groups, region, and place of death. Results: A total of 163 384 deaths were identified from 1999 to 2023. The AAMR increased from 2.22 to 4.32, surging in 2021 after a period of sharp rise (APC 13.52%, 2018–2021), before dropping thereafter (APC −7.18%, 2021–2023). Compared with women, men consistently had higher mortality rates (mean AAMR men: 4.45 vs women: 1.52). The non-Hispanic (NH) American Indian/Alaskan Natives reported the highest AAMR (9.35), whereas NH Asian/Pacific Islanders had the lowest (0.93), depicting the racial disparities. Geographic variations were notable, with the West reporting the highest burden (5.13). Most fatalities (63.3%) occurred in healthcare facilities, followed by the decedents’ homes (25.78%), with lower proportions observed in other locations. Conclusion: These findings describe a growing burden of deaths with marked sex, racial/ethnic, and geographic differences that may inform targeted prevention and equitable care delivery.